“In people with type 2 diabetes, the VPS39 gene in the muscle cells is significantly less active than in other people, and the stem cells with lower gene activity do not produce new muscle cells to the same extent. The gene is important when muscle cells absorb sugar from the blood and build new muscle. Our study is the first to link this gene to type 2 diabetes, ”says Charlotte Ling, professor of epigenetics at Lund University who led the study.
In type 2 diabetes, the ability to produce insulin is impaired and patients have chronically high blood sugar. Muscles are generally poor at absorbing sugar from food, and muscle function and strength are impaired in people with type 2 diabetes.
A muscle consists of a mixture of fiber types with different properties. Muscle tissue can form new muscle fibers throughout life. There are also immature muscle stem cells that are activated in connection with injuries or physical activity, for example. In the current study, the researchers wanted to investigate whether epigenetic patterns in muscle stem cells can provide answers as to why impaired muscle function occurs in type 2 diabetes.
Two groups were included in the study: 14 participants with type 2 diabetes and 14 healthy people in a control group. The participants in the groups were compared according to age, gender and BMI (Body Mass Index). The researchers examined epigenetic changes in the muscle stem cells in both groups and also extracted and compared mature muscle cells under exactly the same conditions. In total, they identified 20 genes, including VPS39, whose gene expression was different between groups in both immature muscle stem cells and mature muscle cells. The researchers also compared the epigenetic patterns of muscle cells before and after cell differentiation in both groups.
“Despite the fact that the muscle stem cells of both groups were grown under identical conditions, we were able to determine more than twice as many epigenetic changes in the type 2 diabetes group in the differentiation of muscle stem cells into mature muscle cells. Muscle-specific genes weren’t regulated normally and epigenetics didn’t work the same way in cells from people with type 2 diabetes, ”says Charlotte Ling.
“The study clearly showed that muscle stem cells that lack the function of the VPS39 gene, which is lower in type 2 diabetes, are also unable to produce new mature muscle cells. This is because muscle stem cells that lack VPS39 due to altered epigenetic mechanisms cannot change their metabolism in the same way as muscle stem cells from controls – the cells therefore remain immature or break down and die, ”says Johanna Säll Sernevi, postdoc researcher at Lund University.
To confirm the results, the researchers also used animal models with mice that had reduced levels of the VPS39 gene to mimic the disease. The mice then altered gene expression and decreased the uptake of sugar from the blood into muscle tissue, just like the people with type 2 diabetes.
The comprehensive study is a collaboration between Swedish, Danish and German researchers who believe the results will open new avenues for the treatment of type 2 diabetes.
“The genome, our DNA, cannot be changed, although epigenetics actually does. With this new knowledge, it is possible to change the dysfunctional epigenetics that occurs in type 2 diabetes. For example, regulating proteins, stimulating or increasing the amount of the VPS39 gene could affect the muscles’ ability to regenerate and absorb sugar, ”concludes Charlotte Ling.
